Pharmacokinetic analysis of irinotecan plus bevacizumab in patients with advanced solid tumors
| Autor: | Daniel J. Berg, Peter J. O'Dwyer, S. N. Holden, Sara Kenkare-Mitra, Lu Xu, Neal J. Meropol, Rebecca L. Blanchard, Cynthia S. Spittle, Anne Kearns, Andrew Dorr, Coen Bernaards, Julie Hambleton, Susan McLaughlin, Crystal S. Denlinger, Samuel Litwin, Bert L. Lum, Maryann Redlinger |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Cancer Research Glucuronosyltransferase Bevacizumab Genotype Leucovorin Pharmacology Biology Toxicology Antibodies Monoclonal Humanized Irinotecan Article chemistry.chemical_compound Pharmacokinetics Neoplasms Antineoplastic Combined Chemotherapy Protocols medicine Humans Pharmacology (medical) Drug Interactions Prodrugs neoplasms Active metabolite Aged Polymorphism Genetic Antibodies Monoclonal Leukopenia Prodrug Middle Aged digestive system diseases Gastrointestinal Tract stomatognathic diseases Uridine diphosphate Oncology chemistry Pharmacogenetics Area Under Curve biology.protein Camptothecin Female Fluorouracil therapeutics medicine.drug |
| Zdroj: | Cancer chemotherapy and pharmacology. 65(1) |
| ISSN: | 1432-0843 |
| Popis: | The purpose of this study was to evaluate the effect of bevacizumab on the pharmacokinetics (PK) of irinotecan and its active metabolite. Exploratory analyses of the impact of variability in uridine diphosphate glucuronosyltransferase 1A (UGT1A) genes on irinotecan metabolism and toxicity were conducted.This was an open-labeled, fixed-sequence study of bevacizumab with FOLFIRI (irinotecan, leucovorin, and infusional 5-fluorouracil). Pharmacokinetic assessments were conducted in cycles 1 and 3.Forty-five subjects were enrolled. No difference in dose-normalized AUC(0-last) for irinotecan and SN-38 between irinotecan administered alone or in combination with bevacizumab was identified. Leukopenia was associated with higher exposure to both irinotecan and SN-38. UGT1A1 polymorphisms were associated with variability in irinotecan PK. Gastrointestinal toxicity was associated with UGT1A6 genotype. No other associations between UGT1A genotypes and toxicity were detected.Bevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity. |
| Databáze: | OpenAIRE |
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